ArticleThe Journal of biological chemistry2010
Phosphopeptide screen uncovers novel phosphorylation sites of Nedd4-2 that potentiate its inhibition of the epithelial Na+ channel.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Combined effect of esaxerenone and dapagliflozin on aldosterone-mediated sodium reabsorption and potassium excretion.Frontiers in physiology · 2025Article
- Targeting E3 ubiquitin ligases: a new frontier in idiopathic pulmonary fibrosis treatment.Frontiers in immunology · 2025Review
- Carbon dioxide and MAPK signalling: towards therapy for inflammation.Cell communication and signaling : CCS · 2023Review
- Nedd4-2 binding to 14-3-3 modulates the accessibility of its catalytic site and WW domains.Biophysical journal · 2022Article
- Acetylation, Phosphorylation, Ubiquitination (Oh My!): Following Post-Translational Modifications on the Ubiquitin Road.Biomolecules · 2022Review
- Review
- Metformin Inhibits NaFrontiers in physiology · 2022Article
- Tril dampens Nodal signaling through Pellino2- and Traf6-mediated activation of Nedd4l.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- A Convergent Functional Genomics Analysis to Identify Biological Regulators Mediating Effects of Creatine Supplementation.Nutrients · 2021Article
- Unbiased proteomic screening identifies a novel role for the E3 ubiquitin ligase Nedd4-2 in translational suppression during ER stress.Journal of neurochemistry · 2021Article
- A Fundamental Role for Oxidants and Intracellular Calcium Signals in Alzheimer's Pathogenesis-And How a Comprehensive Antioxidant Strategy May Aid Prevention of This Disorder.International journal of molecular sciences · 2021Review
- E3 Ubiquitin ligase NEDD4 family‑regulatory network in cardiovascular disease.International journal of biological sciences · 2020Review
- βThe Journal of biological chemistry · 2018Article
- Hypercapnia Impairs ENaC Cell Surface Stability by Promoting Phosphorylation, Polyubiquitination and Endocytosis of β-ENaC in a Human Alveolar Epithelial Cell Line.Frontiers in immunology · 2017Article
- Insulin and SGK1 reduce the function of Na+/monocarboxylate transporter 1 (SMCT1/SLC5A8).American journal of physiology. Cell physiology · 2016Article
- Regulation of the epithelial Na+ channel by the mTORC2/SGK1 pathway.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2016Review
- Localisation of 11β-Hydroxysteroid Dehydrogenase Type 2 in Mineralocorticoid Receptor Expressing Magnocellular Neurosecretory Neurones of the Rat Supraoptic and Paraventricular Nuclei.Journal of neuroendocrinology · 2015Article
- Alternatively spliced proline-rich cassettes link WNK1 to aldosterone action.The Journal of clinical investigation · 2015Article
- Harvest and primary culture of the murine aldosterone-sensitive distal nephron.American journal of physiology. Renal physiology · 2015Article
- Akt recruits Dab2 to albumin endocytosis in the proximal tubule.American journal of physiology. Renal physiology · 2014Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
The E3 ubiquitin ligase Nedd4-2 regulates several ion transport proteins, including the epithelial Na(+) channel (ENaC). Nedd4-2 decreases apical membrane expression and activity of ENaC. Although it is subject to tight hormonal control, the mechanistic basis of Nedd4-2 regulation remains poorly understood. To characterize regulatory inputs to Nedd4-2 function, we screened for novel sites of Nedd4-2 phosphorylation using tandem mass spectrometry. Three of seven identified Xenopus Nedd4-2 Ser/Thr phosphorylation sites corresponded to previously identified target sites for SGK1, whereas four were novel, including Ser-293, which matched the consensus for a MAPK target sequence. Further in vitro and in vivo phosphorylation experiments revealed that Nedd4-2 serves as a target of JNK1, but not of p38 MAPK or ERK1/2. Additional rounds of tandem mass spectrometry identified two other phosphorylated residues within Nedd4-2, including Thr-899, which is present within the catalytic domain. Nedd4-2 with mutations at these sites had markedly inhibited JNK1-dependent phosphorylation, virtually no ENaC inhibitory activity, and significantly reduced ubiquitin ligase activity. These data identify phosphorylatable residues that activate Nedd4-2 and may work together with residues targeted by inhibitory kinases (e.g. SGK1 and protein kinase A) to govern Nedd4-2 regulation of epithelial ion transport.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.